Hypomethylation of Tumor necrosis factor-like cytokine 1A(TL1A) and its decoy receptor 3 expressive level increase has diagnostic value in HBV-associated cirrhosis.

For patients with cirrhosis, early diagnosis is the key to delaying the development of liver fibrosis and improving prognosis. This study aimed to investigate the clinical significance of TL1A, which is a susceptibility gene for hepatic fibrosis, and DR3 in the development of cirrhosis and fibrosis. We analyzed the expression of TL1A, DR3, and other inflammatory cytokines associated with liver fibrosis in serum and PBMCs in 200 patients.TL1A methylation level was lower in patients with HBV-associated LC than in the other groups. In addition, the mRNA level and serum of TL1A and DR3 expression levels were found to increase in the LC. Hypomethylation of the TL1A promoter is present in HBV-associated LC, and TL1A and DR3 are highly expressed in HBV-associated cirrhosis. These results indicate that TL1A and DR3 may play an important role in the pathogenesis of LC and TL1A methylation levels may serve as a noninvasive biomarker for early diagnosis and progression of LC.

A Large Intratemporal Facial Nerve Schwannoma Presenting as an Occluding External Auditory Canal Mass.

Facial nerve schwannomas are rare, benign, slow-growing tumors that can occur in any segment of the facial nerve, although 71% of cases are intratemporal. Surgical resection can lead to facial nerve injury. Facial function recovery after reanimation is usually not better than House-Brackmann (HB) grade III. Thus, for cases of intratemporal facial nerve schwannomas (IFNSs) with favorable facial function (HB grade I or II), observation by periodic magnetic resonance imaging is the mainstay of management. Here, we present a case of a large IFNS with normal facial function in which the mass fully occluded the external auditory canal. The occlusion caused squamous debris to accumulate, potentially leading to cholesteatoma. Faced with this therapeutic dilemma, we chose surgical resection with the patient's informed consent. Stripping surgery was achieved with normal postoperative facial function. There was no postoperative facial paralysis or recurrence at 2-year follow-up. We describe the experience of diagnosis and treatment process for this case, and discuss the possibility of total resection of the tumor with preserving the integrity of facial nerve.

Autologous Costal Cartilage Grafting for a Large Osteochondral Lesion of the Femoral Head: A 1-Year Single-Arm Study with 2 Additional Years of Follow-up.

BACKGROUND: There is currently no ideal treatment for osteochondral lesions of the femoral head (OLFH) in young patients. METHODS: We performed a 1-year single-arm study and 2 additional years of follow-up of patients with a large (defined as >3 cm 2 ) OLFH treated with insertion of autologous costal cartilage graft (ACCG) to restore femoral head congruity after lesion debridement. Twenty patients ≤40 years old who had substantial hip pain and/or dysfunction after nonoperative treatment were enrolled at a single center. The primary outcome was the change in Harris hip score (HHS) from baseline to 12 months postoperatively. Secondary outcomes included the EuroQol visual analogue scale (EQ VAS), hip joint space width, subchondral integrity on computed tomography scanning, repair tissue status evaluated with the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score, and evaluation of cartilage biochemistry by delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) and T2 mapping. RESULTS: All 20 enrolled patients (31.02 ± 7.19 years old, 8 female and 12 male) completed the initial study and the 2 years of additional follow-up. The HHS improved from 61.89 ± 6.47 at baseline to 89.23 ± 2.62 at 12 months and 94.79 ± 2.72 at 36 months. The EQ VAS increased by 17.00 ± 8.77 at 12 months and by 21.70 ± 7.99 at 36 months (p < 0.001 for both). Complete integration of the ACCG with the bone was observed by 12 months in all 20 patients. The median MOCART score was 85 (interquartile range [IQR], 75 to 95) at 12 months and 75 (IQR, 65 to 85) at the last follow-up (range, 24 to 38 months). The ACCG demonstrated magnetic resonance properties very similar to hyaline cartilage; the median ratio between the relaxation times of the ACCG and recipient cartilage was 0.95 (IQR, 0.90 to 0.99) at 12 months and 0.97 (IQR, 0.92 to 1.00) at the last follow-up. CONCLUSIONS: ACCG is a feasible method for improving hip function and quality of life for at least 3 years in young patients who were unsatisfied with nonoperative treatment of an OLFH. Promising long-term outcomes may be possible because of the good integration between the recipient femoral head and the implanted ACCG. LEVEL OF EVIDENCE: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Protective effect of autophagy on endoplasmic reticulum stress induced apoptosis of alveolar epithelial cells in rat models of COPD.

During the present study, we explored the protective effects of autophagy on endoplasmic reticulum (ER) stress (ERS) induced apoptosis belonging to alveolar epithelial cells (AECs) in rat models with chronic obstructive pulmonary disease (COPD). Fifty-six 12-week-old male Sprague-Dawley (SD) rats were randomly assigned into the COPD group (rats exposed to cigarette smoke (CS)), the 3-methyladenine (3-MA) intervention group (COPD rats were administrated with 10 mg/kg autophagy inhibitors), the chloroquine (CQ)-intervention group (COPD rats were administrated 40 mg/kg CQ), and the control group (rats breathed in normal saline). The forced expiratory volume in 0.3 s/forced vital capacity (FEV0.3/FVC%), inspiratory resistance (RI), and dynamic lung compliance (Cdyn) were measured and recorded. The expressions of PKR-like ER kinase (PERK) and CCAAT/enhancer-binding protein-homologous protein (CHOP) were detected by immunohistochemistry. The cell apoptotic rates of AECs were analyzed by terminal deoxynucleotidyl transferase (TdT) mediated dUTP-biotin nick end-labeling (TUNEL) staining. The expression levels of light chain 3 (LC3-II), p62, Beclin-1, ATG5, ATG7, Caspase-12, and Caspase-3 were detected by Western blotting. Results showed that the COPD group exhibited a lower FEV0.3/FVC% and Cdyn, and a higher RI than the control group. Compared with the control group, the integrated optical density (IOD) values of PERK and CHOP, the apoptotic rate of AECs, and expressions of LC3-II, Beclin-1, ATG5, ATG7, Caspase-3, and Caspase-12 expressions were significantly higher, whereas p62 expression was significantly lower in the COPD group. Based on the results obtained during the present study, it became clear that the inhibition of autophagy could attenuate the ERS-induced apoptosis of AECs in rats with COPD.

[Anterolateral minimally-invasive total hip arthroplasty: a clinical comparative study of 110 cases].

OBJECTIVE: To explore the indications and key points of anterolateral minimally-invasive total hip arthroplasty. METHODS: 110 baseline indexes matched patients admitted for unilateral total hip arthroplasty were randomly assigned to 2 equal groups to undergo surgery through a short anterolateral incision of < or = 10 cm or a standard posterolateral incision. All operations were done by the same surgeon. The demographic data, perioperative indexes, and postoperative function indexes were recorded and statistically analyzed. RESULTS: No significant differences were detected with respect to operation time, abduction angle, anteversion angle, stem alignment, and stem fixation between these 2 groups. The incision length, blood loss, perioperative transfusion, and 100 - mm visual analogue pain scale (VAS) score at the first 24 hours of the anterolateral approach group were (7.49 +/- 0.86) cm, (376.18 +/- 168.30) ml, (410.09 +/- 136.46) ml, and (30.76 +/- 21.77) respectively, all significantly shorter, less, or lower than those of the standard posterolateral approach group [(15.2 +/- 1.8) cm, (605.0 +/- 225.1) ml, (629.5 +/- 232.9) ml, and (50.3 +/- 13.7) respectively, all P < 0.01]. The Harris hip score and Barthel index 3 months after operation of the anterolateral approach group were (83.80 +/- 5.64) and (93.45 +/- 6.37) respectively, both significantly higher than those of the standard posterolateral approach group [(75.0 +/- 7.5) and (94.6 +/- 7.5) respectively, both P < 0.01)], however, there were not significant differences in the Harris hip score and Barthel index 3 years after operation between these 2 groups. CONCLUSIONS: Fewer traumas, less blood loss and rapid recovery can be obtained through this new total hip arthroplasty approach. But experienced doctors and special instruments are prerequisite.

Amelioration of osteoarthritis by intra-articular hyaluronan synthase 2 gene therapy.

Osteoarthritis (OA) is a chronic, degenerative disorder of multifactorial aetiology, characterized by loss of articular cartilage and periarticular bone remodelling. Goals of managing OA include controlling pain, maintaining and improving function and health-related quality of life, and limiting functional impairment. Although several managements had been proved to ameliorate the symptoms of osteoarthritis, no methods could cure it thoroughly. High-molecular-weight hyaluronan (HMW-HA) is a major component of synovial joint fluids which physically acts as a viscous lubricant for slow joint movements and as an elastic shock absorber during rapid movements. It also has a variety of biologic effects in vivo, such as inhibiting the release of inflammatory factors and suppressing the degradation of cartilage matrix. Intra-articular injection of synthetic HMW-HA has been used as viscosupplement for knee OA and its therapeutic efficacy has been verified. However, repeated injections of HMW-HA which is needed to control symptoms increase the probability of infection and sometimes there will have acute joint pain with effusion, which requires aspiration to exclude sepsis. In order to overcome the disadvantages of repeated injections of HMW-HA, novel strategies should be developed. As HMW-HA is synthesized by hyaluronan synthase-2 (HAS2), we postulate that HAS2 gene could be delivered into intra-articular cells by methods of gene therapy to achieve long-lasting synthesis of HMW-HA. In our opinion, this strategy seems to hold interesting future prospects for the treatment of OA.

Morphological changes of roof of subacromial bursa in patients with rotator cuff tear.

OBJECTIVE: To investigate the morphological changes of the roof of the subacromial bursa (SAB) and its involvement extent after rotator cuff tear. METHODS: In the experimental group, the roof of SAB was obtained from 30 cases of rotator cuff tear both at the tear site and a site 2.5-3.0 cm distal to the tear site during rotator cuff repair. In the control group, the roof of SAB was obtained from the exposed site of recurrently dislocated shoulder or fractured humeral shaft of 8 cases. The specimens were stained with hematoxylin and eosin and observed under a transmission electron microscope. The cell number was quantitated through counting the blue-stained nucleus in SAB with a computer image analysis system. RESULTS: The number of cells increased significantly in the roof of SAB in the experimental group compared with that of the control group. However, no difference of the bursal reaction was found among the type of rotator cuff tear, the bursa thickness and the presence of fluid in the bursa. The great majority of cells were type B cells observed under the transmission electron microscope. CONCLUSIONS: The increase in cell number in the roof of SAB in the experimental group is a reactive increase rather than an inflammatory process and the involvement of SAB is not limited in extent. The change of the roof of SAB is a secondary reaction to the rotator cuff tear.

[Construction and identification of recombinant adenovirus vector containing Tet-on adjustable NT3 and BDNF genes].

AIM: To construct Tetracycline(tet) inducible recombinant adenovirus vectors containing human neurotrophin 3(NT3) and brain-derived neurotrophic factor(BDNF) genes, respectively and perform PCR and restrictive enzyme digestion analysis. METHODS: Full length NT3 and BDNF cDNAs were subcloned into pIND vector, followed by being cloned into pTRE-shuttle2 vector. The NT3 and BDNF gene fragments resulted from the pTRE-shuttle2-NT3 and pTRE-shuttle2-BDNF digested with I-Ceu I and PI-Sce I were linked to the linear adeno-X virus DNA. The recombinant adenovirus vectors were confirmed by PCR and restriction enzyme digestion analysis. RESULTS: The PCR identification showed that a given band with 312 bp, and predictive fragments proved by restriction enzyme digestion analysis were exhibited. All the above results indicated that human NT3 and BDNF genes had been connected with pAdeno-X vectors correctly. CONCLUSION: Tet inducible recombinant adenovirus vector of Human NT3 and BDNF genes have been constructed successfully, which upon packaged in HEK293 cells, will be used to introduce the target genes into Schwann's cells in-vitro or in-vivo.

Expression of adenovirus-mediated neurotrophin-3 gene in Schwann cells of sciatic nerve in rats.

OBJECTIVE: To investigate the expression of neurotrophin-3 (NT-3) gene in Schwann cells of rat sciatic nerve introduced by an adenovirus vector in vivo. METHODS: A recombinant adenovirus vector for NT-3 (Ad-NT-3) was propagated in 293 packaging cells and titered with tissue culture infectious dose(50) (TCID(50)). Ad-NT-3 was injected directly into the rat sciatic nerve after transection and immediate repair. Immunohistochemical staining was employed to determine the expression of NT-3 in Schwann cells in rat sciatic nerve and the expressive intensity of the tissue slices of the sciatic nerve was measured with LEICA M550 image analysis system. RESULTS: On the 2nd day after injection of Ad-NT-3, positive stain in the Schwann cells was apparent in the vicinity of anastomosis. NT-3 expression increased significantly on the 7th day (P<0.01) and then decreased 14-28 days after injection (P<0.01). There was no significant difference of NT-3 expression between the 14th and 28th day groups (P<0.05). Compared with the 2nd day group, the 14th and 28th day groups still maintained a relatively high level of NT-3 (P<0.01). Intact and repaired nerves, which were injected with adenovirus encoding LacZ genes (Ad-LacZ) or physiological saline served as controls, showed no NT-3-positive Schwann cells. CONCLUSIONS: An adenovirus vector can be used to induce efficiently the expression of NT-3 gene in Schwann cells of rat peripheral nerves following nerve injury and repair, which suggests that neurotrophic factors can be introduced into Schwann cells with an adenovirus vector to promote peripheral nerve regeneration.